The treatment landscape for hematologic malignancies has changed since the recent approval of highly effective CAR-T. Chimeric antigen receptor T-cell therapy (CAR-T) is a type of immunotherapy in which a patient’s T cells are collected and genetically engineered to improve their ability to recognize and kill cancer cells. However, several issues are still unsolved and represent the challenges for the coming years. The lack of initial responses and early relapse are some hurdles to be tackled. Moreover, new strategies are needed to increase the safety profile or shorten the manufacturing process during CAR-T cells therapy production. Finally, the clinical experience with CAR-T cells for solid tumors has been less encouraging, and development in this setting is desirable.